Whole genome sequencing in adolescent idiopathic scoliosis cohort implicates multiple biological pathways

Adolescent idiopathic scoliosis (AIS) is a complex genetic disorder. This study used whole-genome sequencing (WGS) to investigate the genetic basis of AIS in 119 patients from 103 families. Our WGS analysis identified known pathogenic or protein-truncating variants in 15 probands, and other strong or moderate candidate variants in 69 additional patients. We found both coding and non-coding mutations, including structural variants. Candidate genes included known AIS genes (e.g., COL11A2, FBN1) and genes linked to other musculoskeletal disorders with scoliosis (e.g., RYR1). Association analysis confirmed four known AIS single-nucleotide polymorphisms in our cohort. Gene set enrichment analysis revealed four gene clusters related to skeletal muscle contraction, extracellular matrix, and gene expression regulation. This WGS-based approach identified clinically relevant genetic variations and biological pathways in AIS patients, offering valuable insights into its complex development.